Studies on the biological activity of triiodothyronine sulfate

Hepatic microsomes and isolated hepatocytes in short term culture desulfate T₃ sulfate (T₃SO₄). We, therefore, wished to determine whether T₃SO₄ could mimic the action of thyroid hormone in vitro. T₃SO₄ had no thyromimetic effect on the activity of Ca²⁺-ATPase in human erythrocyte membranes at doses up to 10,000 times the maximally effective dose of T₃ (10^-10 mol/L). In GH₄C₁ pituitary cells, T₃SO₄ failed to displace [¹²⁵I]T₃ from nuclear receptors in intact cells or soluble preparations. Thus, T₃SO₄ was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis. Thyroid hormones inhibit [³H]glycosaminoglycan synthesis by cultured human dermal fibroblasts, and T₃SO₄ displayed about 0.5% the activity of T₃ at 72 h. Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes. Propylthiouracil (50 μmol/L) did not affect the action of T₃SO₄, suggesting that deiodination was not important for this activity of T₃SO₄. Thus, it appears T₃SO₄ has no intrinsic biological activity, but, under certain circumstances, may be reactivated by desulfation.